Characterization of Phenethyl Cinnamamide Compounds from Hemp Seed and Determination of Their Melanogenesis Inhibitory Activity

Jae Kwon Kim; Hee-Young Heo; SeonJu Park; Haheon Kim; Jeong Ju Oh; Eun-Hwa Sohn; Se-Hui Jung; Kooyeon Lee

doi:10.1021/acsomega.1c04727

Characterization of Phenethyl Cinnamamide Compounds from Hemp Seed and Determination of Their Melanogenesis Inhibitory Activity

ACS Omega. 2021 Nov 19;6(47):31945-31954. doi: 10.1021/acsomega.1c04727. eCollection 2021 Nov 30.

Authors

Jae Kwon Kim¹, Hee-Young Heo¹, SeonJu Park², Haheon Kim¹, Jeong Ju Oh¹, Eun-Hwa Sohn³, Se-Hui Jung^{1

4}, Kooyeon Lee^{1

4}

Affiliations

¹ Department of Bio-Health Technology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
² Chuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon 24341, Republic of Korea.
³ Department of Herbal Medicine Resource, Institute of Bioscience and Biotechnology, Kangwon National University, Samcheok 25949, Republic of Korea.
⁴ Research Institute, K-medichem Co., Ltd., Chuncheon 24341, Republic of Korea.

Abstract

Hyperpigmentation is induced by the overactivation of tyrosinase, which is a rate-limiting enzyme in melanogenesis. The defatted extract of hemp (Cannabis sativa L.) seed is known to have inhibitory effects on melanogenesis; however, effective compounds in the extract have not been identified yet. In this study, three phenethyl cinnamamides present in hemp seed extract were prepared by purification and chemical synthesis and were assessed for their inhibitory effect on melanogenesis in B16F10 melanoma cells. A comparison of the anti-melanogenesis and anti-tyrosinase activity of hemp seed solvent fractions revealed that the ethyl acetate fraction possessed the greatest potential for suppressing melanogenesis in melanoma cells by decreasing tyrosinase activity. We tentatively identified 26 compounds in the ethyl acetate fraction by comparing spectroscopic data with the literature. Three phenethyl cinnamamides such as N-trans-caffeoyltyramine, N-trans-coumaroyltyramine, and N-trans-feruloyltyramine present abundantly in the ethyl acetate fraction were prepared and their anti-melanogenesis and anti-tyrosinase activities in melanoma cells were evaluated. We found that N-trans-caffeoyltyramine and N-trans-feruloyltyramine inhibited alpha melanocyte stimulating hormone (α-MSH)-induced melanogenesis without cytotoxicity, while N-trans-coumaroyltyramine inhibited melanogenesis with cytotoxicity. IC₅₀ values of N-trans-caffeoyltyramine, N-trans-feruloyltyramine, and N-trans-coumaroyltyramine for inhibition of α-MSH-mediated tyrosinase activation were 0.8, 20.2, and 6.3 μM, respectively. Overall, N-trans-caffeoyltyramine possessed the strongest anti-melanogenesis activity among the three phenethyl cinnamamides evaluated. The inhibitory effect of N-trans-caffeoyltyramine was verified by determining the melanin content and tyrosinase activity in melanoma after treating the cells with synthetic compounds. Thus, N-trans-caffeoyltyramine isolated from hemp seed extract could be useful in cosmetics as a skin-whitening agent.